This project aims at the analysis of various cell surface properties of metastatic tumors which determine tumor cell dissemination and metastatic growth by controlling immune and nonimmune interactions between the tumor cells and the tumor-bearing organism. Thus, the expression, structure and immunogenicity of MHC gene products on cells of metastatic tumors, and particularly on metastatic clones derived from such tumors as distinct from nonmetastatic clones, will be studied. Subsequently, induced alterations in MHC expression will be attempted, to test the effects of such alterations on the metastatogenic potency of the tumor cells. We previously demonstrated the acquisition of metastatic capacity by a nonmetastatic plasmacytoma, following somatic hybridization with normal B\lymphocytes. We shall study further to what extent the cell type of the normal fusion partner determines (a) whether or not metastatic properties will be conferred on a nonmetastatic tumor cell and (b) which would be the target organ for the spontaneous metastasis. We shall define the properties of the normal partner which confer the metastatic properties on the tumor cell. We shall continue our previous studies on the function of NK cells in controlling metastases formation, by testing how general is the correlation between susceptibility to NK cells of cloned tumor cell populations and their metastatic competence. We also shall test whether this applies to primary tumors. The metastatic potential of tumors induced and/or tested in NK-deficient Bg/Bg mice will clarify this question. Finally, the mechanisms by which the local tumor suppresses the growth of its own spontaneous metastases will be analyzed experimentally. We shall test whether primary chemically induced tumors also exert such a suppressive effect, and whether once we unfold its mechanism, we could devise methods to amplify this suppression, and thus experimentally control the progression of metastases. We shall also investigate our observation that general anesthesia applied during tumor surgery accelerates postsurgical development of metastases. We shall investigate whether the anesthetic drugs function via suppressing compartments of the host's immune system, or whether they act directly on the disseminated tumor cells. We then shall search for molecules which would retain anesthetic function, but be devoid of the accelerating effects of tumor metastases.